Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys

A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus...

Natural killer cells and CD4+ T-cells modulate collateral artery development

OBJECTIVE - The immune system is thought to play a crucial role in regulating collateral circulation (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease. Here, we studied the role of lymphocytes in a murine model of hindlimb ischemia. METHODS AND RESULTS - Lymphocytes, detected with markers for NK1.1,...

Interferon-β therapy reduces CD4+ and CD8+ T-cell reactivity in multiple sclerosis

Therapy with interferon-β (IFN-β) has well-established clinical effects in multiple sclerosis (MS), albeit the immunomodulatory mechanisms are not fully understood. We assessed the prevalence and functional capacity of CD4+ and CD8+ T cells in healthy donors, and in untreated and IFN-β-treated MS patients, in response to myelin oligodendrocyte...

Non-invasive measurement of brain damage in a primate model of multiple sclerosis

Early recognition of whether a product has potential as a new therapy for treating multiple sclerosis (MS) relies upon the quality of the animal models used in the preclinical trials. The promising effects of new treatments in rodent models of experimental autoimmune encephalomyelitis (EAE) have rarely been reproduced in patients suffering from...

Analysis of allelic expression patterns of IL-2, IL-3, IL-4, and IL-13 in human CD4+ T cell clones

The occurrence of monoallelic expression of cytokine genes in single cells has been convincingly demonstrated, but there have been few reports of this phenomenon in T cell clones. Here we describe studies on the expression of alleles of the human genes encoding IL-2, IL-3, IL-4, and IL-13 in human CD4+ T cell clones. In contrast to the results...

Organotin-induced apoptosis occurs in small CD4+CD8+ thymocytes and is accompanied by an increase in RNA synthesis

The organotin compounds di-n-butyltin dichloride (DBTC) and tri-n-butyltin chloride (TBTC) induce thymus atrophy in rats. At low doses they inhibit immature thymocyte proliferation, whereas at higher doses in particular TBTC induces apoptotic cell death. In vitro, a similar concentration-effect relationship was observed, i.e. low concentrations...

Intestinal T lymphocytes of different rat strains in immunotoxicity

In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytcs, an inventory was made of single and organized lymphocytes in the epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 344, and Lewis rats. The single and organized lymphocytes were examined microscopically. In addition, the...

Mechanisms of immunotherapeutic intervention by anti-CD40L (CD154) antibody in an animal model of multiple sclerosis

Relapsing experimental autoimmune encephalomyelitis (R-EAE) in the SJL mouse is a Th1-mediated autoimmune demyelinating disease model for human multiple sclerosis and is characterized by infiltration of the central nervous system (CNS) by Th1 cells and macrophages. Disease relapses are mediated by T cells specific for endogenous myelin epitopes...

CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-γ production and increased sensitivity to dexamethasone

A disturbed hypothalamus-pituitary-adrenal gland axis and alterations at the immune system level have been observed in patients with chronic fatigue syndrome (CFS). Glucocorticoids are known to modulate T cell responses; therefore, purified CD4 T cells from CFS patients were studied to determine whether they have an altered sensitivity to...

An epitope delivery system for use with recombinant mycobacteria

We have developed a novel epitope delivery system based on the insertion of peptides within a permissive loop of a bacterial superoxide dismutase molecule. This system allowed high-level expression of heterologous peptides in two mycobacterial vaccine strains, Mycobacterium bovis bacille Calmette- Guerin (BCG) and Mycobacterium vaccae. The...

CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis

We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Activated helper T cells expressing CD40L (gp39) surface protein were found in MS patient brain sections, but not in brain tissue sections of normal controls or patients with other neurological diseases....

The in vivo effects of neutralizing antibodies against IFN-γ, IL-4, or IL-10 on the humoral immune response in young and aged mice

In the present study we investigated whether age-related changes in the composition and functional properties of murine CD4+ T cells are reflected in vivo by a changed humoral response to influenza vaccine in aged mice. After the primary immunization, the titers of influenza-specific IgM, IgG1, IgG2a, and IgG2b, but not of IgG3 and IgE, were...

Differential sensitivity of human naive and memory CD4+ T cells for dexamethasone

Human CD45RA+ ('naive') and CD45RO+ ('memory') CD4+ T cells were compared with respect to their sensitivity to dexamethasone (DEX). In three different activation pathways, i.e. (i) immobilized anti-CD3, (ii) immobilized anti-CD3 plus soluble anti-CD28 and (iii) soluble anti-CD2 plus soluble anti-CD28, naive CD4+ T cells appeared more sensitive...

Enrichment for Th1 cells in the Mel-14+ CD4+ T cell fraction in aged mice

CD4+ T cells from young and aged mice were sorted into Mel-14+ cells which are regarded as naive cells and Mel-14- cells which are regarded as memory cells. These subsets were stimulated in short-time cultures with anti-CD3 or anti-CD3/anti-CD28 in order to determine the presence of Th1 and/or Th2 cytokines. Based on the simultaneous production...

Abrogation of the suppressive effects of dexamethasone by PKC activation or CD28 triggering

The suppressive effect of the glucocorticoid dexamethasone (DEX) on purified CD4+ T cells was found to depend on the activation pathway. In contrast to anti-CD3- or PHA-induced T cell proliferation, the alternative pathway of T cell activation, i.e., through anti-CD2 and anti-CD28, appeared largely resistant to DEX. By titrating anti-CD28 or the...

Age-related changes in immune reactivity: The influence of intrinsic defects and of a changed composition of the CD4+ T cell compartment

Aging is accompanied by a decline in immune reactivity which to a major extent can be attributed to changes at the level of the regulatory CD4+ T cells. In addition to evidence pointing to intrinsic defects, resulting in improper responsiveness of lymphocytes, it is likely that many age-related phenomena can be explained by a changed composition...